Cell migration is essential to many physiological processes such as organogenesis or wound healing. In their natural environment, the direction and speed of cell migration is guided by many signals which may be chemical (chemokines) or physical (microenvironment).
In vitro, these phenomena may be reproduced or redirected to impose a direction of migration on cells, for example using chemoattractants, electrical fields, or by modulating the mechanical environment of the cell.
EP-A-1199354 discloses, for example, the formation of a pattern of cells on a surface by chemically controlling the cell migration. In EP-A-1199354, the surface is treated to provide a pre-made pattern consisting of compounds that promote cell growth and other compounds that do not promote cell growth. Cell culturing is then initiated on this pre-made pattern. However, the effectiveness of the control of cell migration by such a system depends mainly on the choice of chemical compounds promoting or preventing cell growth according to the nature of the cultured cells.
US 2007/0009572 describes a method for preparing a micro- or nanotextured biodegradable film comprising channels whose width can vary from 10 μm to 160 μm, on which muscle cells are deposited. Tests show that the muscle cells are aligned relative to each other along the channels, and their morphology changes to assume an elongated form. The aim of this method is not to migrate cells in a preferred direction but to encourage their alignment with each other to obtain a regular cell stack.
US 2009/02481445 also describes a method for guiding the orientation of cells in a three-dimensional structure, using a surface comprising a micro-channel or a series of micro-channels that are parallel to each other, of greater width than the cells to allow the cells to enter them and having an arbitrary cross-section. As in the previous document, the purpose of this method is not to migrate cells in a preferred direction, but to facilitate their alignment with each other.
Mahmud et al. (Nature Physics 2009, 4, pp. 606) propose adhesive ratchet-shaped patterns to guide cell migration. The effect observed is based on a difference in adhesion between the adhesive portions of the channels and the non-adhesive portions of a substrate such that, when the quality of the difference between the adhesive and non-adhesive areas deteriorates over time, guidance of the cell migration is no longer observed. In addition, the linear or ratchet-shaped adhesion in the channels only holds the cells on these adhesive patterns, meaning in a single dimension in a three-dimensional space, and does not allow, for example, tissue organization on a two-dimensional surface. Finally, the patterns described in Mahmud et al. are always perpendicular to the plane formed by the surface carrying the cells.
These methods for redirecting the natural phenomena of cell migration can also have applications in vivo.
US 2009/0093879 proposes an implant having micro- or nanometric three-dimensional patterns on the surface. These patterns allow controlling the adhesion of micro-organisms or fibroblasts to the surface of the implant when it is placed in a living being, thus improving wound healing. US 2009/0093879 suggests that the surface micro- or nanostructures can guide the cells that begin the healing process, allowing them to organize in an ordered manner on the surface of the implant.
However, the control of cell migration in a given direction could also have medical applications which do not involve the forced organization of cells around an implant, such as the directed migration of cells to the surface of a wound or the creation of artificial organs in tissue engineering.
There is therefore a need for new devices for guiding cell migration in a chosen direction, whose effectiveness does not depend on the type of moving cell considered, and which are simple to implement, are minimally invasive for tissues, and remain robust over time.
Guiding cell migration is understood to mean, in the sense of the present application, that the cells are encouraged to migrate in one direction rather than in any other. In other words, guiding the migration breaks the migration symmetry in the direction considered. “Guiding” the cell migration differs from “orienting” the cell migration, the latter being where the cells preferentially migrate in two opposite directions without one of these directions being favored over the other.